SLS-004 is a Gene Therapy Program Targeting the Regulation of the SNCA Gene, Which Encodes Alpha-synuclein (α-synuclein)

The system is based on CRISPR-dCas9 fused with the catalytic domain of DNA methyltransferase 3A (DNMT3A), an enzyme that is responsible for DNA methylation

The system was delivered to dopaminergic neurons derived from human induced pluripotent stem cells (hiPSCs) from a PD patient

As a result, the expression of SNCA was modified and disease-related cellular-phenotypes characteristics of the neurons were reversed

About Alpha-synuclein

Alpha-synuclein (α-synuclein) is a protein whose function in the healthy brain is currently

Alpha-synuclein (also α-synuclein) is a protein which is of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies and Lewy neurites, protein clumps that are the pathological hallmark of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA)

In the several years since its discovery, alpha-synuclein has been the focus of intensive efforts by basic Parkinson's disease researchers working to definitively characterize the protein's role in Parkinson's and its potential as a target for neuroprotective therapies

SNCA Gene and SLS-004

At present, there is no effective treatment to prevent PD or halt its progression

The SNCA gene, which encodes alpha-synuclein expression, has been implicated as a highly significant risk factor for PD

Accumulating evidence suggests that elevated levels of wild-type alpha-synuclein are causative in the pathogenesis of PD

The role of SNCA overexpression in PD pathogenesis and the need to maintain normal physiological levels of alpha-synuclein protein emphasize the so-far unmet need to develop new therapeutic strategies, such as SLS-004, targeting the regulatory mechanisms of SNCA expression